Pro- and anti-inflammatory cytokines: the hidden keys to autoimmune gastritis therapy DOI Creative Commons

Greta Cascetta,

Giorgia Colombo,

Gianmarco Eremita

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Aug. 13, 2024

Autoimmune gastritis (AIG) is an autoimmune disorder characterized by the destruction of gastric parietal cells and atrophy oxyntic mucosa which induces intrinsic factor deficiency hypo-achlorhydria. AIG predominantly affects antral with patients experiencing increased inflammation a predisposition toward development adenocarcinoma type I neuroendocrine tumors. The exact pathogenesis this incompletely understood although dysregulated immunological mechanisms appear to major contributors. This review gastritis, unmet medical need, summarizes current knowledge on pro- anti-inflammatory cytokines strategies for discovery novel biomarkers potential pharmacological targets.

Language: Английский

The central role of IL-33/IL-1RL1 pathway in asthma: From pathogenesis to intervention DOI Creative Commons
Akshaya Keerthi Saikumar Jayalatha, Laura Hesse, Maria E. Ketelaar

et al.

Pharmacology & Therapeutics, Journal Year: 2021, Volume and Issue: 225, P. 107847 - 107847

Published: April 2, 2021

Interleukin-33 (IL-33), a member of the IL-1 family, and its cognate receptor, Interleukin-1 receptor like-1 (IL-1RL1 or ST2), are susceptibility genes for childhood asthma. In response to cellular damage, IL-33 is released from barrier tissues as an ‘alarmin’ activate innate immune response. drives type 2 responses by inducing signalling through IL-1RL1 in several structural cells, thereby leading cytokine chemokine production. gene transcript encodes different isoforms generated alternative splicing. Its soluble isoform, IL-1RL1-a sST2, acts decoy sequestering IL-33, inhibiting IL1RL1-b/IL-33 signalling. therefore considered putative biomarkers targets pharmacological intervention This review will provide overview genetics biology IL-33/IL-1RL1 pathway context asthma pathogenesis. It discuss potential complexities targeting how may inform precision medicine this pathway, possible positioning therapeutics expanding landscape novel biologicals applied management.

Language: Английский

Citations

109
Molecular Targets for Biological Therapies of Severe Asthma DOI Creative Commons
Corrado Pelaia, Claudia Crimi, Alessandro Vatrella

et al.

Frontiers in Immunology, Journal Year: 2020, Volume and Issue: 11

Published: Nov. 30, 2020

Asthma is a heterogeneous respiratory disease characterized by usually reversible bronchial obstruction, which clinically expressed different phenotypes driven complex pathobiological mechanisms (endotypes). Within this context, during the last years several molecular effectors and signalling pathways have emerged as suitable targets for biological therapies of severe asthma, refractory to standard treatments. Indeed, various therapeutic antibodies currently allow intercept at levels chain pathogenic events leading type 2 (T2) airway inflammation. In addition pro-allergic immunoglobulin E (IgE), that chronologically represents first molecule against an anti-asthma monoclonal antibody (omalizumab) was developed, today other are successfully exploited treatments asthma. particular, pro-eosinophilic interleukin 5 (IL-5) can be targeted mepolizumab or reslizumab, whereas benralizumab selective blocker IL-5 receptor. Moreover, dupilumab behaves dual receptor antagonist pleiotropic interleukins 4 (IL-4) 13 (IL-13). Besides these drugs already available in medical practice, biologics under clinical development such those targeting innate cytokines, also including alarmin thymic stromal lymphopoietin (TSLP), plays key role pathogenesis Therefore, ongoing future significantly changing global scenario asthma management. These new options make it possible implement phenotype/endotype-specific treatments, delineating personalized approaches precisely addressing individual traits pathobiology. Such tailored strategies thus allowing target immune-inflammatory responses underlying uncontrolled T2-high

Language: Английский

Citations

102
Adult‐onset eosinophilic airway diseases DOI Open Access
Koichiro Asano, Shigeharu Ueki, Mayumi Tamari

et al.

Allergy, Journal Year: 2020, Volume and Issue: 75(12), P. 3087 - 3099

Published: Oct. 11, 2020

Abstract Eosinophilic airway inflammation is one of the cardinal features allergic diseases such as atopic asthma and rhinitis. These childhood‐onset conditions are mediated by allergen allergen‐specific IgE often accompanied other including food allergy eczema. They can develop consecutively in same patient, which referred to an march. In contrast, some phenotypes asthma, nonsteroidal anti‐inflammatory drugs‐exacerbated disease (N‐ERD), chronic rhinosinusitis with nasal polyps (CRSwNP)/eosinophilic CRS bronchopulmonary aspergillosis/mycosis (ABPA/ABPM) adult‐onset diseases, characterized prominent peripheral blood eosinophilia. Most these conditions, except for ABPA/ABPM, nonatopic, coexistence multiple eosinophilic systemic disease, granulomatosis polyangiitis (EGPA), common. this review, we focus on eosinophil biology, genetics clinical characteristics pathophysiology N‐ERD, CRSwNP/eosinophilic CRS, ABPA/ABPM EGPA, while exploring common genetic, immunological pathological among diseases.

Language: Английский

Citations

83
Current Insights into Immunology and Novel Therapeutics of Atopic Dermatitis DOI Creative Commons

Hidaya A. Kader,

Muhammad Azeem,

Suhib A. Jwayed

et al.

Cells, Journal Year: 2021, Volume and Issue: 10(6), P. 1392 - 1392

Published: June 4, 2021

Atopic dermatitis (AD) is one of the most prevalent inflammatory disease among non-fatal skin diseases, affecting up to fifth population in developed countries. AD characterized by recurrent pruritic and localized eczema with seasonal fluctuations. initializes phenomenon atopic march, during which infant patients are predisposed progressive secondary allergies such as allergic rhinitis, asthma, food allergies. The pathophysiology complex; onset caused several factors, including strong genetic predisposition, disrupted epidermal barrier, immune dysregulation. was initially defects innate system a vigorous skewed adaptive Th2 response environmental agents; there compelling evidences that disorder involves multiple pathways. Symptomatic palliative treatment only strategy manage restore integrity. Researchers trying more precisely define contribution different genotypes elucidate role various axes. In this review, we have summarized current knowledge about roles responsive cells AD. addition, novel strategies for management comprehensively described, some ongoing clinical trials promising therapeutic agents. This information will provide an asset towards identifying personalized targets better outcomes.

Language: Английский

Citations

66
Immune activation in irritable bowel syndrome: what is the evidence? DOI
Javier Aguilera‐Lizarraga, Hind Hussein, Guy E. Boeckxstaens

et al.

Nature reviews. Immunology, Journal Year: 2022, Volume and Issue: 22(11), P. 674 - 686

Published: March 16, 2022

Language: Английский

Citations

61
Tezepelumab: A Potential New Biological Therapy for Severe Refractory Asthma DOI Open Access
Corrado Pelaia, Giulia Pelaia, Claudia Crimi

et al.

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(9), P. 4369 - 4369

Published: April 22, 2021

Thymic stromal lymphopoietin (TSLP) is an innate cytokine, belonging to the group of alarmins, which plays a key pathogenic role in asthma by acting as upstream activator cellular and molecular pathways leading type 2 (T2-high) airway inflammation. Released from epithelial cells upon tissue damage induced several noxious agents including allergens, viruses, bacteria, airborne pollutants, TSLP activates dendritic lymphoid involved pathobiology T2-high asthma. Tezepelumab fully human monoclonal antibody that binds TSLP, thereby preventing its interaction with receptor complex. Preliminary results randomized clinical trials suggest tezepelumab characterized good safety efficacy profile patients severe, uncontrolled

Language: Английский

Citations

60
Comparative efficacy of tezepelumab to mepolizumab, benralizumab, and dupilumab in eosinophilic asthma: A Bayesian network meta-analysis DOI Creative Commons
Tanawin Nopsopon,

Grace Lassiter,

Ming‐Li Chen

et al.

Journal of Allergy and Clinical Immunology, Journal Year: 2022, Volume and Issue: 151(3), P. 747 - 755

Published: Dec. 17, 2022

Language: Английский

Citations

42
Molecular and cellular mechanisms of itch and pain in atopic dermatitis and implications for novel therapeutics DOI Creative Commons
Shawn G. Kwatra, L. Misery, Claire Clibborn

et al.

Clinical & Translational Immunology, Journal Year: 2022, Volume and Issue: 11(5)

Published: Jan. 1, 2022

Atopic dermatitis is a chronic inflammatory skin disease. Patients with atopic experience lesions associated intense itch and pain, which lead to sleep disturbance poor mental health quality of life. We review the molecular mechanisms underlying pain symptoms in discuss current clinical development treatments for moderate-to-severe dermatitis. The pathology includes aberrant immune activation involving significant cross-talk among neuronal cells. Exogenous endogenous triggers modulate stimulation mediators including cytokine/chemokine expression/release by cells, causes inflammation, barrier disruption, growth sensory neurons, pain. These complex interactions cell types are mediated primarily cytokines, but also involve chemokines, neurotransmitters, lipids, proteases, antimicrobial peptides, agonists ion channels or various G protein-coupled receptors. have cytokine profile characterised abnormal levels interleukins 4, 12, 13, 18, 22, 31 33; thymic stromal lymphopoietin; interferon gamma. Cytokine receptors mainly signal through Janus kinase/signal transducer activator transcription pathway. Among emerging novel therapeutics, several kinase inhibitors being developed topical systemic treatment because their potential expression release. changes gene that favourable effects on local release, probably other mediators, thus successfully modulating responsible

Language: Английский

Citations

39
The evolving landscape of biologic therapies for atopic dermatitis: Present and future perspective DOI
Eden David, Benjamin Ungar, Yael Renert‐Yuval

et al.

Clinical & Experimental Allergy, Journal Year: 2023, Volume and Issue: 53(2), P. 156 - 172

Published: Jan. 18, 2023

Abstract Atopic dermatitis (AD) is one of the most common, chronic inflammatory skin diseases with a significant physical, emotional and socioeconomic burden. In recent years understanding AD pathogenesis has expanded from Th2‐centred perspective, recognition involvement other immune axes. different endotypes, influenced by environment, genetics race, transcriptomic profiles have identified differing contributions multiple axes such as, Th17, Th22 Th1. The enriched pathogenic model catalysed development numerous biologic therapies targeting range key molecules implicated in disease progression. Currently, dupilumab tralokinumab, which both target Th2 pathway, are only approved for United States Europe. New development, however, Th2‐pathway along cytokines axes, including Th17 Th22, offering promise varied treatments this heterogeneous disease. As pipeline advances, integration into clinical practice approval these experimental biologics may provide more effective, tailored therapeutic solutions illuminate on pathologic processes across broader, diverse patient population.

Language: Английский

Citations

30
The Role of TSLP in Atopic Dermatitis: From Pathogenetic Molecule to Therapeutical Target DOI Creative Commons
Jialiang Luo, Zhengyumeng Zhu,

Yumeng Zhai

et al.

Mediators of Inflammation, Journal Year: 2023, Volume and Issue: 2023, P. 1 - 8

Published: April 15, 2023

Atopic dermatitis (AD) is a kind of chronic skin disease with inflammatory infiltration, characterized by barrier dysfunction, immune response dysregulation, and dysbiosis. Thymic stromal lymphopoietin (TSLP) acts as regulator response, positively associated AD deterioration. Mainly secreted keratinocytes, TSLP interacts multiple cells (including dendritic cells, T mast cells), following induction Th2-oriented during the pathogenesis AD. This article primarily focuses on biological function, relationship between different cell populations, treatments targeting TSLP.

Language: Английский

Citations

30